Prostate cancer is the most prevalent disease affecting males in many Western countries, with an estimated 29,480 deaths in 2014 in the US alone. Incidence rates for prostate cancer deaths have been decreasing since the early 1990s in men of all races/ethnicities, though they remain about 60% higher in African Americans than in any other group. The relationship between dietary polyphenols and the prevention of prostate cancer has been examined previously. Although results are sometimes inconsistent and variable, there is a general agreement that polyphenols hold great promise for the future management of prostate cancer. Various dietary components, including polyphenols, have been shown to possess anti-cancer properties. Generally considered as non-toxic, dietary polyphenols act as key modulators of signaling pathways and are therefore considered ideal chemopreventive agents. Besides possessing various anti-tumor properties, dietary polyphenols also contribute to epigenetic changes associated with the fate of cancer cells and have emerged as potential drugs for therapeutic intervention. Polyphenols have also been shown to affect post-translational modifications and microRNA expressions. This article provides a systematic review of the health benefits of selected dietary polyphenols in prostate cancer, especially focusing on the subclasses of polyphenols, which have a great effect on disease prevention and treatment.

Epithelial-to-mesenchymal transition (EMT) plays an important role in prostate cancer (PCa) metastasis. The transcription/translation regulatory Y-box binding protein-1 (YB-1) is known to be associated with cancer metastasis. We observed that YB-1 expression increased with tumor grade and showed an inverse relationship with E-cadherin in a human PCa tissue array. Forced YB-1 expression induced a mesenchymal morphology that was associated with down regulation of epithelial markers. Silencing of YB-1 reversed mesenchymal features and decreased cell proliferation, migration and invasion in PCa cells. YB-1 is activated directly via Akt mediated phosphorylation at Ser102 within the cold shock domain (CSD). We next identified fisetin as an inhibitor of YB-1 activation. Computational docking and molecular dynamics suggested that fisetin binds on the residues from β1 - β4 strands of CSD, hindering Akt's interaction with YB-1. Calculated free binding energy ranged from −11.9845 to −9.6273 kcal/mol. Plasmon Surface Resonance studies showed that fisetin binds to YB-1 with an affinity of approximately 35 μM, with both slow association and dissociation. Fisetin also inhibited EGF induced YB-1 phosphorylation and markers of EMT both in vitro and in vivo. Collectively our data suggest that YB-1 induces EMT in PCa and identify fisetin as an inhibitor of its activation.

Conjugated linoleic acid (CLA) is found naturally in dairy and beef products at levels of 0.2% to 2% of the total fat. A more concentrated source of dietary CLA, low in saturated fat, would be highly desirable to obtain optimum CLA levels of about 3 g/d. We recently reported photoisomerization of soy oil with iodine catalysis to be a simple way of producing CLA in laboratory without high-energy input or expensive enzymes and microorganisms. However, a long irradiation time of 144 h has been a limitation for this technique to be of practical value. The objectives of this study were to build a pilot plant unit to rapidly produce high-CLA soy oil by photoirradiation and optimize the processing parameters to obtain high-CLA soy oil. Degassed oil with dissolved-iodine catalyst was irradiated by UV lamps in an illuminated laminar flow unit (ILFU). The ILFU consists of 2 borosilicate glass plates in a silicone lined stainless steel frame. The static mode of operation yielded 5.7% of total CLA isomers and performed twice as well than the continuous mode with 2.5% of total CLA. Irradiating oil in a static mode with reflective surfaces increased the CLA yields 3-fold to 16.4%. About 22% of total CLA isomers can be rapidly produced from soy oil linoleic acid with 0.35% iodine catalyst in a 0.5-cm-thick oil layer maintained at 48 degrees C for 12 h. The peroxide value and GC-MS analysis did not identify any volatile compounds characteristic of lipid oxidation. This study is a definitive step toward the commercialization of large-scale production of CLA-rich soy oil.

Cancer remains a major public health concern and a significant cause of death worldwide. Identification of bioactive molecules that have the potential to inhibit carcinogenesis continues to garner interest among the scientific community. In particular, flavonoids from dietary sources are the most sought after because of their safety, cost-effectiveness, and feasibility of oral administration. Emerging data have provided newer insights into understanding the molecular mechanisms that are essential to identify novel mechanism-based strategies for cancer prevention and treatment. Dietary flavonoid fisetin (3,3′,4′,7-tetrahydroxyflavone) found in many fruits and vegetables has been shown in preclinical studies to inhibit cancer growth through alteration of cell cycle, inducing apoptosis, angiogenesis, invasion, and metastasis without causing any toxicity to normal cells. Although data from in-vitro and in-vivo studies look convincing, well-designed clinical trials in humans are needed to conclusively determine the efficacy across various cancers. This review highlights the chemopreventive and therapeutic effects, molecular targets, and mechanisms that contribute to the observed anticancer activity of fisetin against various cancers.

The incidence of melanoma continues to rise. Inspite of treatment advances, the prognosis remains grim once the disease has metastasized, emphasizing the need to explore additional therapeutic strategies. One such approach is through the use of mechanism-based dietary intervention. We previously showed that the flavonoid fisetin inhibits melanoma cell proliferation, in vitro and in vivo. Here, we studied fisetin-mediated regulation of kinases involved in melanoma growth and progression. Time-course analysis in 3-D melanoma constructs that transitioned from radial to vertical growth showed that fisetin treatment resulted in significant decrease in melanocytic lesions in contrast to untreated controls that showed large tumor nests and invading disseminated cells. Further studies in melanoma cultures and mouse xenografts showed that fisetin-mediated growth inhibition was associated with dephosphorylation of AKT, mTOR and p70S6K proteins. In silico modeling indicated direct interaction of fisetin with mTOR and p70S6K with favorable free energy values. These findings were validated by cell-free competition assays that established binding of fisetin to p70S6K and mTOR while little affinity was detected with AKT. Kinase activity studies reflected similar trend with % inhibition observed for p70S6K and mTOR at lower doses than AKT. Our studies characterized, for the first time, the differential interactions of any botanical agent with kinases involved in melanoma growth and demonstrate that fisetin inhibits mTOR and p70S6K through direct binding while the observed inhibitory effect of fisetin on AKT is mediated indirectly, through targeting interrelated pathways.